The long-term goal is to understand variation for quantitative traits in terms of the individual loci (QTLs) affecting them. Many inherited human diseases are quantitative traits. The specific aims are to determine whether alleles at loci with major morphological effects contribute to quantitative variation in natural populations, and to determine the extent and nature of the association between molecular and quantitative genetic variation at these loci. The model system to be used is the number of abdominal and sternopleural bristles in Drosophila melanogaster. Divergent artificial selection lines for sternopleural and abdominal bristle number will be started from a natural population and selected to the limit. The effects of the major chromosomes on selection response will be addressed. Chromosome substitution lines, in which a viable major chromosome of large effect from a high selection line is made homozygous and substituted into the homozygous low selection line background, will be made for each major chromosome, for both selected traits. The six chromosome substitution lines will be used to construct recombinant inbred lines, in which chromosome from the high selection line is recombined with chromosome from the low selection line. The bristle numbers and recombination breakpoints will be determined for each recombinant inbred line, the latter using cytological locations of roo transposable elements, which will differ between high and low parental chromosomes. The numbers, effects, and locations of QTLs affecting the bristle traits will be estimated. The effects of nine cloned major loci which affect bristle development on quantitative variation in bristle number in a natural population will be assessed. Wild type regions from each of these loci from 50 chromosomes of a natural population will be substituted into a common isogenic background, and their contribution to genetic variation in bristle number estimated. Restriction map variation will be determined for the nine loci, and associations between molecular polymorphisms and phenotypic effects will be examined.